a phase i/ii pilot study of simultaneously administered rhu gm-csf ( cho cell ) and azidothymidine ( azt ) in patients with severe hiv infection and leukopenia: pharmacokinetics and feasibility

Conditions: HIV Infections; Cytopenias

Summary: to assess the safety and efficacy of subcutaneously administered sargramostim ( granulocyte-macrophage colony-stimulating factor; gm-csf ) in increasing and maintaining the neutrophil count in hiv-infected adults who have developed neutropenia as a result of receiving the antiretroviral agent, zidovudine ( azt ). to assess the safety and efficacy of subcutaneously administered gm-csf in increasing and maintaining the neutrophil count in hiv-infected adults with pre-existing neutropenia who are at high risk of developing hematologic intolerance while receiving the antiretroviral agent, azt, for the first time. to assess the potential therapeutic benefit of concomitant gm-csf and azt on the natural history of hiv infection and associated infectious complications.


Eligibility criteria:
inclusion criteria concurrent treatment: allowed: * minimal local irradiation for tumors. patients must have: * diagnosis of aids or aids related complex (arc). * neutropenia, due either to zidovudine (azt) or hiv infection. * life expectancy = or \> 6 months. exclusion criteria co-existing condition: patients with the following conditions or symptoms are excluded: * significant malabsorption as defined by greater than 10 percent weight loss and one or more of the following: * serum carotene less than 75 iu/ml. * vitamin a level less than 75 iu/ml. * more than 4 foul-smelling or greasy stools per day. * other criteria of malabsorption. * kaposi's sarcoma (ks) or other tumor which is likely to require specific antitumor therapy during study, other than minimal local irradiation. * active, life-threatening infection with bacterial, viral, fungal, or protozoan pathogens or fever of 39 degrees c within 10 days of study entry, unless it is apparent that the fever is not due to a severe underlying infection. concurrent medication: excluded within 4 weeks of study entry: * any investigational drug. * immunomodulating agents. * hormonal therapy. * cytolytic chemotherapeutic agents. * antiretroviral agent other than zidovudine (azt). * excluded within 4 months of study entry: * suramin. * excluded within 3 months of study entry: * ribavirin. patients with the following are excluded: * significant malabsorption. * tumor likely to require specific antitumor therapy during study. * other significant medical problems and conditions specified in patient exclusion co-existing conditions. * uncorrected nutritional deficiencies that may contribute to neutropenia. * hypersensitivity to zidovudine (azt) or other nucleoside analogs. * profound dementia or altered mental status that would prohibit the giving of informed consent. prior treatment: excluded within 1 month of study entry: * transfusion. * excluded within 4 weeks of study entry: * radiation therapy to greater than 100 cm2 body area. current drug or alcohol abuse. unprotected sexual behavior or other activities which might introduce a new inoculation of hiv during the study. patients must be willing to refrain from unprotected sexual or other activities which might introduce a new inoculum of hiv during the study.

Keywords: neutropenia drug interactions granulocyte-macrophage colony-stimulating factor acquired immunodeficiency syndrome zidovudine